1. BLOOD TRANSFUSION THERAPY
PRESENTED BY-DR.NITIN SHANKER
MODERATOR-DR.B.KAUR

2. BENEFITS Enhanced oxygen carrying capacity
Improved homeostasis with blood component therapy
Volume support of Cardiac output

3. BLOOD COMPONENT THERAPY
Whole blood
Packed Red Blood Cell
Leukoreduced Red Blood Cell
Fresh Frozen Plasma
Cryoprecipitate
Platelet concentrate
Prothrombin Complex
Single Donor Plasma

4. PACKED RED BLOOD CELL
Contain same amount of Haemoglobin as whole blood, but much of plasma has been removed.
Haematocrit 70%,whereas whole blood 40%
Reconstituted with 5% Dextrose,0.4% saline,5% Dextrose in 0.9% saline,0.9% saline and Normosol-R with a ph of 7.4.

5. STORAGE OF BLOOD
Citrate phosphate Dextrose Adenine (CPDA-1) anticoagulant preservative in which Blood stored at 1 degree celsius-6 degree celsius
Addition of Adenine to CPD solution allows RBC to synthesize ATP and extend storage time from 21 days to 45 days.
Shelf life can be further extended to 42 days AS-1(Adsol),AS-3(Nutricel) or AS-5(Optisol)
Citrate-anticoagulant,phosphate-buffer,dextrose-red cell energy source
Adsol-Adenine,Glucose,mannitol and sodium chloride,citrate hct-70%
Nutricel-Glucose,Adeninine,Citrate,Phosphate,Sodium chloride and mannitol
Optisol-Dextrose,Adenine,sodium chloride and mannitol

6. INDICATION FOR TRANSFUSION
The Practice Guidelines for Blood Component Therapy developed by the American society of Anaesthesiologists (ASA) state that “red blood cell transfusion is rarely indicated when the hemoglobin concentration is greater than 10 g/dl and is almost always indicated when it is less than 6 g/dl”

7. COMPENSATORY MECHANISMS DURING ANEMIA
Increased Cardiac output
Redistribution of Cardiac output
Increased Oxygen extraction
Changes in Oxygen-Hemoglobin affinity

8. COMPARISON OF WHOLE BLOOD AND PACKED RED BLOOD CELL
VALUE
WHOLE BLOOD
PACKED RED
BLOOD CELL
Volume(ml)
517
300
Erythrocyte mass (ml)
200
Hematocrit(%) 40 70
Albumin(g)
12.5 4
Globulin(g)
6.25 2
Total Protein(g)
48.8 36
Plasma sodium(meq) 45 15
Plasma Potassium (meq)
Plasma Acid (meq) 80 25
Donor-to-recepient ratio
1 unit per patient
1 unit per 4-6 patients

9. CONDITIONS THAT MAY DECREASE RBC TRANSFUSION THRESHOLD
Impaired oxygenation
Pulmonary disease
High altitude
Increased oxygen demand
Hyperthermia
Hyperthyroidism
Sepsis
Pregnancy

10. Contd….. Limited ability to increase Cardiac Output
Coronary artery disease
Myocardial dysfunction
β-Adenergic Bloackade
Inability to redistribute cardiac output
Low SVR states
Occlusive vascular disease
Left shift of Oxygen-Haemoglobin curve

11. Contd…. Abnormal Haemoglobins
Presence of recently transfused Hb (decreased 2,3-DPG)
Hb S (sickle cell disease)
Acute Anemia (limited 2,3-DPG compensation)
Ongoing or imminent blood loss
Traumatic/surgical bleeding
Placenta previa or accreta,abruption,uterine atony
Clinical coagulopathy

12. PLATELET CONCENTRATES
Prepared by differential centrifugation of whole blood or by plateletpheresis techniques.
Stored at room temperature;satisfactorily kept for 7 days.
Platelet concentrate transfusion,third leading cause of transfusion-related deaths (following sepsis).
One unit of platelet concentrate will increase platelet count of a 70-kg recepient by ,000/µL;One apheresis unit →30,000-60,000/µL

13. INDICATIONS FOR TRANSFUSION
American Society of Anesthesiologists (ASA) Task force recommendations:
Prophylatic platelet transfusion is ineffective and rarely indicated when thrombocytopenia is due to increased platelet destruction (eg.idiopathic thrombocytic purpura)
Prophylatic platelet transfusion rarely indicated in surgical patients with thrombocytopenia due to decreased platelet production when platelet count >1,00,000 and usually indicated when platelet count > 50,000

14. INDICATIONS FOR TRANSFUSION contd….
Surgical and obstretic patients with microvascular bleeding usually require platelet transfusion if platelet count >1,00,000 and usually indicated platelet count <50,000;Therapy to be based upon patients bleeding risk.
Vaginal deliveries or operative procedures ordinarily associated with insignifcant blood loss maybe undertaken in patients with platelet count <50,000.
Platelet transfusion maybe indicated despite an apparently adequate platelet count if there is known platelet dysfunction and microvascular bleeding.

15. FRESH FROZEN PLASMA
Contains all plasma proteins particularly factors ν and νιιι
ASA task force recommended the administration of FFP with the following guidelines:
For urgent reversal of Warfarin therapy;dosage 5-8ml/kg
For correction of known coagualation factor deficiencies for which specific correlates are unavailaible

16. FRESH FROZEN PLASMA contd..
For correction of microvascular bleeding secondary to coagulation factor deficiency in patients transfused with more than 1 blood volume and when prothrombin and partial thromboplastin time cannot be obtained in a timely fashion.
Calculated to achieve a minimum of 30% plasma factor;dosage ml/kg.
Contraindicated for augmentation of plasma volume or albumin concentration.

17. INDICATIONS FOR FFP ADMINISTRATION
Replacement of isolated factor deficiencies
Reversal of Warfarin effect
Antithrombin ιιι deficiency
Treatment of immunodeficiencies
Treatment of thrombotic thrombocytopenic purpura
Massive blood transfusion(when factors ν and νιιι < 25% normal)
Requirements of above points if PT atleast 1.5 times longer than normal

18. CRYOPRECIPITATE
Precipitate that remains when FFP thawed slowly at 4 degree celsius
Primarily contains factor νιιι and fibrinogen;also has Von Willebrand factor and fibronectin
All other plasma proteins in trace
Used in Haemophillia A and fibrinogen deficiency treatment.

19. CRYOPRECIPITATE contd….
ABO compatibility not must.
Administered within 6 hours after thawing.
One unit increases fibrinogen levels by 5-7 mg/dL

20. COMPLICTIONS OF BLOOD TRANSFUSION
Development of various infections
Transfusion associated reactions(Hemolytic transfusion reaction)
Transfusion related lung injury
Left shift of oxygen dissociation curve
Coagulopathy noticed with massive transfusions
K meq in stored blood on day

21. COMPLICATIONS OF BLOOD TRANSFUSION contd….
Dilutional Thrombocytopenia
Low levels of factor ν and νιιι
Disseminated Intravascular Coagulation like syndrome
Citrate Intoxication and Hyperkalemia
Hypothermia
Acidosis
Transfusion associated Graft versus Host Disease
Adverse ocular reaction
Transfusion related immunomodulation

22. RISKS OF BLOOD TRANSFUSION
Type Occurrence in Red Blood Cell Units Transfused
Infectious
Human immunodeficiency virus in 1.4–2.4×106
Hepatitis B in 58,000–149,000
Hepatitis C in 872,000–1.7× 106
Bacterial infection in 2,000
Immunologic reactions
Febrile nonhemolytic transfusion reactions in 100
Anaphylactic transfusion reactions in 20,000–50,000
ABO mismatch
Hemolysis in 60,000
Death in 600,000
Leukocyte-related target organ injury in 20 to 1 in 50
Transfusion-related acute lung injury in 2000
Post-transfusion purpura Rare
Transfusion services error in 14,000

23. HEMOLYTIC TRANSFUSION REACTIONS
Signs and symptoms:
Chills
Fever
Chest and flank pain
Nausea
Hemoglobinuria
Bleeding diasthesis(noticed during surgery)
Hypotension

24. STEPS IN TREATMENT OF A HEMOLYTIC TRANSFUSION REACTION
STOP THE TRANSFUSION
Maintain urine output at a minimum of ml/hr(generous fluid administration,mannitol,furosemide)
Alkalinize the urine
Assay urine and plasma hemoglobin concentrations
Determine platelet count,partial thromboplastin time and serum fibrinogen levels
Return unused blood to blood bank for repeat cross match
Send patients blood and urine sample to blood bank for examination
Prevent hypotension to ensure adequate renal blood flow

26. BLOOD CONSERVATION STRATEGIES

27. BLOOD CONSERVATIONS
Increasing interest in in Blood conservation since last 15 years
Significant risks of allogenic blood transfusion.
Shortage of allogenic blood
Patient choice
Improvement in availaibilty of transfusion alternatives.

28. HIGH RISK PREDICTORS Advanced age
Low preoperative red blood cell volume
(preoperative anemia or small body size)
Preoperative antiplatelet or antithrombotic drug
Reoperative or complex procedures
Emergency operations
Noncardiac patient comorbidities

29. INTERVENTIONS TO LIMIT BLOOD TRANSFUSION
Pharmacologic agents:
Hemostatic Drugs with Antifibrinolytic Properties
Erythropoetin
DDAVP
Recombinant factor 7 A
Devices to Aid Blood conservation:
Cell Saver
Ventilator-assisted Blood Conservation PEEP
Oxygenator types
Perfusion Blood Pumps
Heparin Bonded Circuits
Leukocyte Filtration

30. INTERVENTIONS TO LIMIT BLOOD TRANSFUSION contd….
Perfusion techniques and OPCAB
Heparin Management
Protamine dosing
Acute Normovolemic Hemodilution
Preoperative autologous Blood transfusion
Minimized extracoporeal bypass circuits
Retrograde autologous priming
Hemofiltration
Off-pump procedures for Blood conservation
Topical agents/Tissue Glues

31. PHARMACOLO-GICAL AGENTS

32. Antifibrinolytic agents:
Aprotonin
Serine protease inhbhitor
Binds with serine protease inhibhitors:
Trypsin Decreasing
Plasmin Affinity
Plasmin kallikrein
Tissue kallikrein
Elastase
Urokinase
Thrombin

33. Aprotonin: Pharmocokinetics: Inactive via oral route
Rapid distribution into extravascular space
Following redistribution plasma half life aprox.150 mins
Less than 10% excreted as unchanged drug
Slowly degraded as lysosomal enzymes
Terminal elimination phase half life-10 hr

34. Aprotonin: Mechanism of action:
Inhibhits serine proteases that attenuates:
Inflammatory responses
Fibrinolysis
Thrombin generation
Inhibhits pro-inflammatory cytokine release and maintains glycoprotein homeostasis

35. Aprotinin- Mechanism of Action
Blood/Surface activation
Intrinsic Pathway
Plasmin
Kallikrein
Heparin
Non Specific Serine Antiprotease:Aprotinin
Complement activation
Clotting
Fibrinolysis
Kinins
Cytokines/ Adhesion Molecules
Systemic Inflammatory response

36. Aprotonin-dosage:
1-2 million KIU followed by a continous infusion of 100, ,000 KIU/hr

37. Aprotonin: Adverse effects: Hypersenstivity Graft occlusion
Heart failure
Renal Dysfunction
Stroke

38. Lysine Analogues: Epsilon Amino Caproic Acid Tranexemic acid MOA:
They inhibit plasminogen by binding to the lysine binding sites on the plasminogen molecule.
Spare platelet function by inhibiting the deleterious effects of plasmin.
Tranexamic acid is similar in action to Epsilon-aminocaproic acid but it is approximately 10 times more potent.

39. Lysine Analogues: Dose:
Intravenous loading dose of 10 mg/kg for tranexamic acid followed by 1 mg/kg/hr
mg/kg of ε-aminocaproic acid followed by infusions of 25 mg/kg/hr

40. Erythropoeitin:
Endogenous glycoprotein-stimulates red cell production in response to hypoxia and anemia.
Recombinant EPO: Reduce preoperative anaemia in patients undergoing autologous blood donation
Safe and effective
Drawbacks
Expensive
Hypertension
Lag period: 4-6 days-less effective post operatively
Beta blockers and cardiopulmonary bypass inhibit effect
Dose
U/kg s/c or I/v 3 times a week

41. Desmopressin (DDAVP):
Releases
Endogenous factor VIII precursors
Von Willebrand factor
Tissue type plasminogen activator.
Not helpful prophylactically to reduce bleeding after cardiac procedures.
Helpful in patients with demonstrable and specific platelet dysfunction known to respond to this agent (eg, uremic or CPB-induced platelet dysfunction, type I von Willebrand’s disease).
Dose
0.3 μg/kg iv, sc or intranasal

42. Recombinant Factor VIIa:
Vitamin K-dependent glycoprotein
Currently FDA approved only for the treatment of severe bleeding episodes in hemophiliacs with factor inhibitors or patients with FVII deficiency
Binds to tissue factor→ Activation of factor X (FXa) on the platelet surface (a phospholipid surface);
FXa + Activated factor V→ prothrombinase complex → Thrombin formation.

43. Recombinant Factor VII a:
Plasma concentrations ~50 nM→ partial Thrombin Generation
Plasma concentrations ~ 100 to 150 nM → Full activation of Thrombin (Thrombin burst)
Recommended dose for bleeding in hemophiliac patients is 90 µg/kg i.v.
Doses for the treatment of uncontrolled hemorrhage varied from 15 to 180 µg/kg i.v
Recommended as rescue therapy for severe intractable bleeding without an identifiable surgical source that is unresponsive to routine approaches after cardiac procedures using CPB.

44. DEVICES

45. Cell Salvage Techniques:
Advantages
Disadvantages
↓ risk of infection
↓ risk of transfusion reaction
Safer in patients with rare blood groups & multiple antibodies
No immunosuppression
? Acceptable to Jehovah’s Witnesses
↓ demand for allogenic blood products
↑ cost- setup cost inc. staff training
Unused blood wasted
↑ risk of bacterial contamination

46. Ventilator-assisted Blood Conservation:
Positive End Expiratory Pressure
Increased end-expiratory airway pressure (PEEP) exerts mechanical pressure on the myocardium and may limit microvascular bleeding after heart surgery.
Use of prophylactic PEEP postoperatively is not effective.

47. Oxygenator Type:
Membrane oxygenator systems during cardiopulmonary bypass are preferred for reduction in blood utilization and improved safety.
Advantages
Fewer cerebral emboli
Better biocompatibility
Reduced blood utilization

48. HEPARIN-BONDED CIRCUITS:
Heparin coating of the oxygenator or of the entire bypass circuit
Limits platelet activation
Reduces complement activation
Alters cellular adhesion to the bypass tubing
Diminishes the inflammatory pulmonary injury seen after CPB
Need of Low dose Heparin & consequently reduced protamine dose

49. PERFUSION TECHNIQUE

50. ACUTE NORMOVOLEMIC HEMODILUTION (INTRAOPERATIVE AUTOLOGOUS DONATION):
Removal of one to two units of blood immediately before surgery
To maintain circulating blood volume, the volume is replaced with crystalloid / colloid.
Contraindications:
Evolving acute myocardial infarction
Unstable angina
Cardiogenic shock
Preoperative anemia
Sepsis
known bacteremia.
Relative contraindications
Low EF (< 30%)

51. ACUTE NORMOVOLEMIC HEMODILUTION:
Principle
Lowering the red blood cell concentration (hematocrit) during surgery decreases the reduction in red cell mass lost for any given volume of blood lost.
In cardiac surgery
The blood removed before the institution of CPB is “protected” from the potential deleterious effects of platelet activation and consumption, hemolysis, complement activation, and the production of a variety of inflammatory cytokines associated with extracorporeal circulation

52. PREOPERATIVE AUTOLOGOUS BLOOD DONATION:
Autologous blood donation of as much as 2 units a few days to a few weeks preoperatively.
Not routinely employed in cardiac surgery, because of possible increase in the incidence of myocardial infarction or hemodynamic instability.
Useful in carefully selected (mostly elective) patients particularly when coupled with appropriately dosed erythropoietin therapy and/or iron therapy.

53. Contraindications to participation in autologous Blood Donation programmes:
Evidence of infection and risk of bacteremia
Scheduled surgery to correct Aortic Stenosis
Unstable angina
Active Seizure disorder
Myocardial Infarction or CVA within 6 months of donation
Patients with significant Cardiac or Pulmonary disease
High grade left main coronary artery disease
Cyanotic heart disease
Uncontrolled hypertension

54. Advantages/Disadvantages
Prevents transfusion transmitted disease
Prevents red cell alloimmunization
Supplements the blood supply
Provides compatible-blood for patients
Prevents some adverse transfusion reactions
Provides reassurance to patients concerned about blood risks
Does not effect risk of bacterial contamination
Does not effect risk of ABO incompatibility error
Is more costly than allogenic blood
Results in wastage of blood not transfused
Increased incdence of adverse reactions
Subjects patients to perioperative anemia and increased likelihood of transfusion

55. Postoperative Blood Collection:
Recovery of blood from surgical drains followed by reinfusion after passing through a microaggrergrate filter (40 µm filter).
Transfusion to be done within 6 hrs of collection.
Volume not to exceed 1400 ml
Low hematocrit value
Practised in cardiac surgeries and following knee arthroplasty.

56. Topical sealants: Fibrin Glue: Blood derivative
Derived from a source of fibrinogen and factor Xlll (fibrinogen stabilizing factor)
Applied directly to the site of bleed

57. WHATS NEW???? Artificial oxygen carriers- Perflurocarbons
Haemoglobin-based oxygen carriers

58. Perflurocarbons:
Simple constructed molecules (MW )derived from cyclic or straight chain hydrocarbons with hydrogen atoms replaced halogens.
Chemically and biologically inert
Oxygen kinetics-linear
Intravenous infusion-taken by RES system
Given low dosages (maximum dose 0f 60% Oxygenat 2.7g/kg)

59. Haemoglobin-based Oxygen carriers:
Originates from outdated Human red cells
Follow sigmoid curve-oxyen kinetics
Due to oncotic properties also termed as plasma expanders

60. THANK YOU